Response to Induction Chemotherapy with Novel Agents Does Not Predict Outcomes of Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation

High dose therapy and autologous hematopoietic cell transplantation (AHCT) is a standard therapy option for at least young (<65 years) and otherwise transplant eligible multiple myeloma (MM) patients. While outcomes of AHCT in Hodgkin's and non-Hodgkin lymphoma patients showing evidence of chemo-sensitive disease pre-transplant are clearly superior, the prognostic significance of pre-AHCT remission status in MM is controversial. Failure to achieve at least a partial remission (PR) in response to induction chemotherapy before AHCT has not been shown to negatively impact transplant outcomes, at least in the pre-thalidomide (Thal)/lenalidomide (Len)/bortezomib (Bor) era (Kumar S, BMT 2004 & Singhal S, BMT 2002). Whether this paradigm holds true for novel agent-containing induction therapies is not known. Recently <50% reduction in ‘serum M-protein’ following induction with Thal or Len based induction therapy has retrospectively been shown to predict poor outcome after AHSCT (Gertz M, Blood 2010). However, data evaluating transplant outcomes relative to pre-transplant remission status assessed by strict IMWG criteria, and data in Bor-based regimens is still scant. We report here the impact pre-transplant remission status on outcomes of AHCT after chemotherapy with novel agents.

The study involves 63 consecutive patients who underwent a planned, single AHCT within 1-year of starting induction chemotherapy with regimens containing Thal, Len, or Bor, between 2000–2009. All patients with normal renal function received uniform conditioning with Mel200 (MEL140 if serum creatinine was >2 mg/dl). The disease response pre- and post transplant was determined by using the IMWG criteria. SPSS version 16.0 was used for statistical analysis. Kaplan-Meier method was used to calculate overall survival (OS) and progression free survival (PFS). Outcomes of patients achieving at least a PR (P-group; n=54) before AHCT were compared with one not achieving at least a PR (NO-P-group; n=9). As an exploratory analysis outcomes of patient achieving at least a very good partial response (VGPR) (V-group; n=40) with ones not achieving at least a VGPR (NO-V-group) was also performed (no-V group; n=23).

The mean age of the patients at transplant was 53yrs (range 44 –72yrs). 68 % (n=43) of patients were male. At diagnosis 42 patients (66%) had Salmon-Durie stage III disease, while 21 (34%) had stage I/II disease. Median Karnofsky performance status was 90. At the time of AHCT, the median HCT-CI score was 0. 33 % (n=21) of the patients received radiation therapy prior to transplant. At a median follow-up of 36 months, the 3 year OS of patients in P-group and NO-P-group was 58% vs. 60% (p=0.93) respectively. The 3 year PFS in similar order was 22% vs. 31% (p=0.74). The 3 year OS of patients in V-group and NO-V-group (44% vs. 62%) was also not significantly different (p=0.53). Respective figures of 3 year PFS are 22% vs. 24% (p=0.72) respectively. 3yr non relapse mortality was 5% for the whole cohort. Of the 31 patients that entered an AHCT with a PR, 15 improved to a CR post transplant, 2 improved their status to a VGPR whereas 14 remained in a PR. A total of 9 patients entered an AHCT with a stable disease (SD) of which 5 advanced to a CR, 3 a PR and one remained in SD. On the other hand of the 6 patients who entered an AHCT with a VGPR, 2 improved to a CR whereas the rest maintained their status. Finally, all the 17 patients entering an AHCT with a CR maintained their status.

Our limited, retrospective data suggest acceptable AHCT outcomes in MM patients who do not achieve at least a PR in response to novel induction chemotherapies pre-transplantation. Failure to achieve a PR following novel induction therapies should not ‘routinely’ preclude consideration for high-dose therapy and AHCT.

Abraham:Genentech: Membership on an entity's Board of Directors or advisory committees. Craig:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamadani:celgene: Honoraria, Speakers Bureau; otsuka: Research Funding, Speakers Bureau.